Exendin-4 Does Not Promote Beta-Cell Proliferation or Survival During the Early Post-Islet Transplant Period in Mice
| Autor: | Doris A. Stoffers, Shaoping Deng, Yong-Suk Bae, Michael F. Crutchlow, Ming Yu |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Blood Glucose
endocrine system Cell Survival medicine.medical_treatment Islets of Langerhans Transplantation Article Diabetes Mellitus Experimental Mice Vascularity Insulin-Secreting Cells Diabetes mellitus medicine Animals Hypoglycemic Agents Transplantation Homologous Mice Inbred BALB C Transplantation geography geography.geographical_feature_category Venoms business.industry medicine.disease Islet Mice Inbred C57BL Transplantation Isogeneic surgical procedures operative Immunosuppressive drug Hyperglycemia Immunology Exenatide Surgery Pancreatic islet transplantation Subrenal Capsule Assay Beta cell medicine.symptom Peptides business medicine.drug |
| Zdroj: | Transplantation Proceedings. 40:1650-1657 |
| ISSN: | 0041-1345 |
| DOI: | 10.1016/j.transproceed.2008.03.161 |
| Popis: | Current pancreatic islet transplantation protocols achieve remarkable short-term success, but long-term insulin independence remains elusive. Hypoxic and inflammatory insults cause substantial early posttransplant graft loss while allo/autoimmunity and immunosuppressive drug toxicity threaten long-term graft mass and function. Exendin-4 (Ex4) is a GLP-1 receptor agonist that promotes beta-cell proliferation, survival, and differentiation. To determine whether Ex-4 displays potential as a graft-supportive agent, we transplanted 500 murine islets under the kidney capsule of syngeneic or allogeneic streptozocin-treated recipient mice and immediately initiated daily treatment with vehicle or Ex4. Graft beta-cell proliferation, death, and vascularity were assessed at 1, 3, and 10 days after syngeneic islet transplantation. For allogeneic recipients, blood glucose and body weight were assessed until glycemic deterioration. Ex-4 did not promote graft beta-cell proliferation, reduce beta-cell death, or enhance graft vascularity over the first 10 days after syngeneic islet transplantation. A trend toward prolongation of posttransplant euglycemia was observed with Ex4 treatment in nonimmune-suppressed allograft recipients, but its use in this setting was associated with frequent, severe hypoglycemia over the first 2 posttransplant days. Our findings do not support a beneficial effect of Ex-4 on islet grafts during the critical early posttransplant period, further, they demonstrate a significant hypoglycemic potential of Ex-4 in the first days after islet transplantation in mice. Optimal application of GLP-1 receptor agonists for long-term proliferative and survival benefits in transplantation may require earlier intervention prior to and/or during islet isolation for peri-transplant cytoprotection and administration beyond the period of engraftment. |
| Databáze: | OpenAIRE |
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